Effective treatment of many illnesses involves the administration of one or more therapeutic drugs. Many therapeutic drugs, however, produce adverse side effects such as nausea and emesis. These side effects often limit the usefulness of the drug and may even render the drug unacceptable for use. For example, the administration of therapeutic doses of many anti-cancer drugs, e.g., cisplatin, is often accompanied by nausea and emesis. Many clinically useful narcotic analgesics such as morphine and related opiates, meperidine, methadone and the like, given to ease pain, also produce nausea and emesis. Apomorphine, a synthetic opiate obtained by treating morphine with hydrochloric acid, is another example of an emetic agent.
U.S. Pat. No. 4,719,215 to Goldberg, incorporated herein by reference, discloses that quaternary derivatives of noroxymorphone, such as methylnaltrexone, are useful for the treatment, both prophylactic and therapeutic, of the nausea and vomiting associated with the administration of narcotic analgesics such as morphine and the like without interfering with the analgesic activity of the drug.
Methylnaltrexone and other quaternary derivatives of noroxymorphone have proven ineffective at relieving nausea and emesis caused by the administration of other emesis-causing agents such as anticancer drugs, apomorphine and the like.